The present invention relates to sensing or determining the concentration of an analyte of interest in a medium. More particularly, the invention relates to sensor apparatus or systems and methods for sensing the concentration of an analyte of interest, for example, carbon dioxide, in a medium, for example, blood. The invention also relates to sensor apparatus or systems and methods for sensing the concentration of an analyte of interest, for example, ammonia, SO.sub.2, or NO.sub.2 in industrial settings and environments.
It is sometimes necessary or desirable for a physician to determine the concentration of certain gases, e.g., oxygen, ionized hydrogen and carbon dioxide, in blood. This can be accomplished utilizing an optical sensor which contains an optical indicator responsive to the component or analyte of interest. The optical sensor is exposed to the blood, and excitation light is provided to the sensor so that the optical indicator can provide an optical signal indicative of a characteristic of the analyte of interest. For example, the optical indicator may fluoresce and provide a fluorescent optical signal as described in Lubbers et al. U.S. Pat. No. Re 31,897 or it may function on the principles of light absorbance as described, for example, in Fostick U.S. Pat. No. 4,041,932.
The use of optical fibers has been suggested as part of such sensor systems. The optical indicator is placed at the end of an optical fiber which is placed in contact with the medium to be analyzed. This approach has many advantages, particularly when it is desired to determine a concentration of analyte in a medium inside a patient's body. The optical fiber/indicator combination can be made sufficiently small in size to easily enter and remain in the cardiovascular system of the patient. Consistent and accurate concentration determinations are obtained.
Optical fluorescence CO.sub.2 sensors commonly utilize an indirect method of sensing based on the hydration of CO.sub.2 to carbonic acid within an optionally buffered aqueous compartment containing a pH sensitive dye. The aqueous compartment is encapsulated in a barrier material which is impermeable to hydrogen ion but permeable to CO.sub.2. An optically interrogated pH change in the internal aqueous compartment can then be related to the partial pressure of CO.sub.2 in the monitored sample. Ionic isolation of the internal aqueous phase may be achieved by directly dispersing aqueous droplets throughout the isolating matrix as described in U.S. Pat. No. 4,824,789 (Yafuso et al.) which is herein incorporated by reference. Alternatively, the aqueous phase may be sorbed into porous particles which are then dispersed throughout the isolating matrix as described in U.S. Pat. No. 4,557,900 (Heitzmann). The isolation matrix or "barrier" is typically a crosslinked silicone polymer. Such sensing chemistries may further comprise aqueous and silane viscosifiers and dispersing aids to stabilize the dispersion prior to crosslinking the silicone polymer.
Unfortunately, a characteristic feature of these types of sensors is reversible "CO.sub.2 conditioning drift" (hereinafter for brevity sometimes referred to as "drift"), a response instability accentuated by large changes in CO.sub.2 partial pressure. FIGS. 3a and 3b show typical drift data for a CO.sub.2 sensor formulation in an ex-vivo blood gas sensing system. FIG. 3a illustrates a typical "intensity" plot, showing the intensity of a dye (e.g., the fluorescence intensity) as a function of time after a step change from a medium equilibrated with air (pCO.sub.2 =0.2 mm Hg) to a medium equilibrated with 6 volume percent CO.sub.2 (pCO.sub.2 =45.6 mm.Hg). FIG. 3b illustrates a plot of "measured" CO.sub.2 concentration (calculated based on a calibration curve correlating CO.sub.2 concentration or partial pressure to either dye intensity or a parameter such as a ratio of dye intensities) as a function of time after a step change from a medium equilibrated with air (pCO.sub.2 =0.2 mm) to a medium equilibrated with 6 volume percent CO.sub.2 (pCO.sub.2 =45.6 mm). If a sensor in thermodynamic equilibrium with air equilibrated buffer (pCO.sub.2 .congruent.0.2 mmHg) is suddenly exposed to an elevated CO.sub.2 level such as a physiological CO.sub.2 level (pCO.sub.2 .congruent.45.6 mm), the measured fluorescence intensity (illustrated in FIG. 3a) will change to a new reading within 1-2 minutes. However, when the sensor is maintained at this elevated CO.sub.2 condition (e.g., pCO.sub.2 .gtoreq.40 mm) for several hours, the measured intensity drifts asymptotically in a direction generally opposite to the initial fast response. This is referred to as "CO.sub.2 conditioning drift." The initial response to elevated CO.sub.2 may be partially or completely regained if the sensor is "deconditioned" for several hours at the baseline state, therefore, the CO.sub.2 conditioning effect is reversible.
This drift instability has been recognized in this type of sensor, although the specific drift mechanism has been in debate. For example, "nonspecific drift" is referred to in U.S. Pat. Nos. 5,246,859 and 4,943,364, and characterized as an instability upon exposure to low or high levels of CO.sub.2. No mechanism causing this drift was postulated in these patents. One proposal put forth to explain CO.sub.2 conditioning drift is outlined by Otto Wolfbeis in "Fiber Optic Chemical Sensors and Biosensors", Vol. 2, Chap. 11-V. Specifically, CO.sub.2 conditioning drift is attributed to a reversible migration of water in and out of the aqueous indicator compartment, driven by a CO.sub.2 dependent mismatch of the osmolarities for the aqueous indicator phase and the external medium being sensed. The CO.sub.2 conditioning drift has thus been attributed to the change in the pH/pCO.sub.2 relationship for the internal aqueous indicator phase as the indicator and buffer concentrations change.
Koch et al., U.S. Pat. No. 4,943,364, disclose a CO.sub.2 sensor which purports to have minimal drift comprising: a hydrolyzed dye/gel polymer; optionally a solution permeable membrane; and a gas-permeable membrane. Koch et al. postulate that the cause of sensor drift in their system is due to the gradual loss of weakly bonded dye molecules from the dye/gel polymer structure. To lessen this problem Koch et al. treat their dye/gel polymer with base to remove weakly bonded dye molecules from the polymer. Unfortunately, sensors of the type described in Koch et al. are expensive to manufacture and difficult to uniformly produce.
Nelson et al., U.S. Pat. No. 5,246,859 discloses a carbon dioxide sensor and method for making carbon dioxide sensors comprising a bicarbonate buffer solution having a concentration of at least 100 mM, a hydroxy pyrene trisulfonic acid pH indicator, and a polyvinylpyrolidone aqueous phase viscosifier. The sensor may be optionally exposed to carbon dioxide gas (between 2 and 100 weight percent) prior to use. The sensor purports not to exhibit non-specific drift.
It would be desirable to provide a sensor which has a fast response time, is free of CO.sub.2 conditioning drift, and is easily manufactured.